# name
Significant geographical differences in prevalence of mutations
                associated with Plasmodium falciparum and Plasmodium vivax drug
                resistance in two regions from Papua New Guinea

# metadata.dc.description.abstract[].value
BACKGROUND: Drug resistance remains a major obstacle to malaria
                treatment and control. It can arise and spread rapidly, and vary
                substantially even at sub-national level. National malaria
                programmes require cost-effective and timely ways of
                characterizing drug-resistance at multiple sites within their
                countries. METHODS: An improved multiplexed post-PCR ligase
                detection reaction-fluorescent microsphere assay (LDR-FMA) was
                used to simultaneously determine the presence of mutations in
                chloroquine resistance transporter (crt), multidrug resistance 1
                (mdr1), dihydrofolate reductase (dhfr) and dihydropteroate
                synthase (dhps) genes in Plasmodium falciparum (n = 727) and
                Plasmodium vivax (n = 574) isolates collected in 2006 from
                cross-sectional community population surveys in two
                geographically distinct regions (Madang and East Sepik) of Papua
                New Guinea (PNG) where strong regional differences in in vivo
                aminoquinoline and antifolate therapeutic efficacy had
                previously been observed. Data were compared to those of a
                follow-up survey conducted in 2010. RESULTS: Despite some very
                low parasite densities, the assay successfully amplified all P.
                falciparum and P. vivax loci in 77 and 69 % of samples,
                respectively. In 2006, prevalences of pfdhfr (59R-108 N) double
                mutation/wild type pfdhps haplotype, pfcrt SVMNT haplotype
                (72S-76T double mutation), and 86Y pfmdr1 mutation all exceeded
                90 %. For P. vivax, 65 % carried at least two pvdhfr mutations,
                97 % the 647P pvdhps mutation and 54 % the 976F pvmdr1 mutation.
                Prevalence of mutant haplotypes was higher in Madang than East
                Sepik for pfcrt SVMNT (97.4 vs 83.3 %, p = 0.001), pfdhfr
                (59R-108 N) (100 vs 90.6 %, p = 0.001), pvdhfr haplotypes (75.8
                vs 47.6 %, p = 0.001) and pvmdr1 976F (71.2 vs 26.2 %, p <
                0.001). Data from a subsequent Madang survey in 2010 showed that
                the prevalence of pfdhps mutations increased significantly from
                <5 % to >30 % (p < 0.001) as did the prevalence of
                pvdhfr mutant haplotypes (from 75.8 to 97.4 %, p = 0.012).
                CONCLUSIONS: This LDR-FMA multiplex platform shows feasibility
                for low-cost, high-throughput, rapid characterization of a broad
                range of drug-resistance markers in low parasitaemia infections.
                Significant geographical differences in mutation prevalence
                correlate with previous genotyping surveys and in vivo trials
                and may reflect variable drug pressure and differences in
                health-care access in these two PNG populations.

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Significant geographical differences in prevalence of mutations
                associated with Plasmodium falciparum and Plasmodium vivax drug
                resistance in two regions from Papua New Guinea